Recyclable Asymmetric Cyclization in Ionic Liquid Catalyzed by an Amino Acid, Leading to a Wieland-Miescher Ketone Analogue

Abstract

A procedure for recyclable asymmetric cyclization leading to optically active Wieland-Miescher ketone analogue has been developed employing d-phenylalanine and d-CSA in [hmim]PF₆ and dimethylimidazolidinone in 81% chemical yield and 74% enantiomeric excess in average after five uses. A Hajos-Wiechert ketone analogue was also synthesized in a similar manner.

Key words

amino acid - asymmetric catalysis - asymmetric synthesis - enones - ionic liquids - supported catalysis

References and Notes

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1

JSPS Research Fellow.

10

Typical Experimental Procedure.
To a solution of the triketone 1 (196 mg, 1 mM) in [hmim]PF₆ (1.8 mL) and DMI (1.2 mL) was added d-Phe (165 mg, 1 mM) and d-CSA (116 mg, 0.5 mM) under nitrogen atmosphere. Reaction temperature was raised from r.t. to 70 °C by 10 °C at 1 h intervals. After being stirred at 70 °C overnight, the product was triturated with Et₂O until the spot of the product 3 in ionic liquid was not observed by TLC monitoring (eluent: EtOAc-n-hexane = 1:1). Evaporation of Et₂O followed by column chromatography and subsequent medium pressure LC of the residue (eluent: EtOAc-n-hexane = 1:1) afforded the enone 3 (167 mg, 87%). After evacuation of Et₂O under reduced pressure, a mixture of d-Phe and d-CSA in [hmim]PF₆ was reused after addition of DMI (1.2 mL). The ee of the product 3 was determined to be 86% by HPLC analysis using chiral column (Daicel AS-H column, eluent: n-hexane-i-PrOH = 9:1).